HBV Reactivation More Severe in HBV/HCV Coinfected Patients Receiving DAA Therapy

It is estimated that 71 million people have a chronic hepatitis C viral (HCV) infection. Furthermore, HCV is predicted to claim the lives of approximately 400,000 individuals each year. Because HCV and the hepatitis B virus (HBV) have shared modes of transmission, it is common to find patients coinfected with both viruses, leading to poor disease prognosis and increased risk of developing liver cirrhosis and liver cancer.

The current standard of care to treat HCV is Direct Acting Antiviral (DAA) therapy, a highly effective regimen that has been shown to cure most HCV patients within 12 weeks. However, there have been concerns about HBV reactivation in patients treated with DAA therapy, prompting the US Food and Drug Administration (FDA), as well as the European Medicine Agency’s Pharmacoviglance Risk Assessment Committee to issue warnings about the risk of reactivation.

In a study published in the Journal of Hepatology, principal investigator George Lau, MD, and his colleagues conducted a systematic review in hopes of determining the efficacy of anti-HCV treatment in chronic HCV patients coinfected with HBV.

The authors conducted an exhaustive literature search, examining studies that used anti-HCV treatments in patients coinfected with HBV/HCV. Studies were excluded if they featured patient populations coinfected with hepatitis A, D, or E or human immunodeficiency virus (HCV). In addition, patients who were concurrently treated for HCV and HBV were also excluded. The endpoint of interest was HBV reactivation, defined as a significant increase in HBV DNA at the end of anti-HCV therapy. The authors separated patients based on HBV status, classifying patients as coinfected with overt HBV (meaning they are positive for HBV surface antigens) or occult HBV (meaning patients were negative for HBV surface antigens and positive for the presence of HBV DNA). Furthermore, two types of anti-HCV therapy were examined, interferon-based (IFN) therapy as well as interferon-free DAA therapy.

The literature search initially yielded 6,224 studies, which were pruned down to a final 36 studies examined. Overall, the studies consisted of 1,185 HBV/HCV coinfected patients, of which 1,037 received 24 to 48 weeks of IFN-based therapy and 148 received 8 to 12 weeks of DAA therapy. In addition, of the 1,185 patients, 889 were coinfected with overt HBV, and the remaining 296 were coinfected with occult HBV.

Dr. Lau and his colleagues found that HBV reactivation occurred earlier in patients treated with DAA therapy than in patients treated with IFN-based therapies. In addition, the authors reported that the HBV reactivation rate in chronic hepatitis C patients coinfected with overt HBV was 14.1%. The authors also report that coinfected patients receiving DAA therapy were at increased risk of developing severe hepatitis and liver failure due to HBV reactivation compared with patients receiving IFN-based therapy.

Overall, the authors report that HBV reactivation occurs earlier and is more severe in patients treated with DAA therapy compared with patients treated with IFN-based therapy. The authors speculate that the cause of HBV reactivation during, or after,anti-HCV treatment could be due to the observation that HCV suppresses HBV. As a consequence, during anti-HCV treatment, the suppression of HBV is now removed, leading to HBV reactivation. This work highlights the importance of screening HCV-positive patients for HBV before initiating anti-HCV treatment, particularly if administering DAA therapy.

Samar Mahmoud graduated from Drew University in 2011 with a BA in Biochemistry and Molecular Biology. After two years of working in industry as a Quality Control Technician for a blood bank, she went back to school and graduated from Montclair State University in 2016 with an MS in Pharmaceutical Biochemistry. She is currently pursuing her PhD in Molecular and Cellular Biology at the University of Massachusetts at Amherst.